Using the Lives Saved Tool to estimate the number of maternal and newborn lives saved by DFID programming: 2011–2015: Technical Note: Version 4

In 2010, the United Kingdom (UK) Government Department for International Development (DFID) announced their ‘Framework for results for reproductive, maternal and newborn health (RMNH)’ which included several ambitious goals in relation to reproductive, maternal and newborn health including saving 250,000 newborn and 50,000 maternal lives by 2015 (1). DFID simultaneously committed to measuring its achievements in reaching these goals. [Introduction

DNA repair in cancer: emerging targets for personalized therapy

Genomic deoxyribonucleic acid (DNA) is under constant threat from endogenous and exogenous DNA damaging agents. Mammalian cells have evolved highly conserved DNA repair machinery to process DNA damage and maintain genomic integrity. Impaired DNA repair is a major driver for carcinogenesis and could promote aggressive cancer biology. Interestingly, in established tumors, DNA repair activity is required to counteract oxidative DNA damage that is prevalent in the tumor microenvironment. Emerging clinical data provide compelling evidence that overexpression of DNA repair factors may have prognostic and predictive significance in patients. More recently, DNA repair inhibition has emerged as a promising target for anticancer therapy. Synthetic lethality exploits intergene relationships where the loss of function of either of two related genes is nonlethal, but loss of both causes cell death. Exploiting this approach by targeting DNA repair has emerged as a promising strategy for personalized cancer therapy. In the current review, we focus on recent advances with a particular focus on synthetic lethality targeting in cancer

A field, petrological and geochemical study of the Masirah Ophiolite, Oman

A reconnaissance survey of the 1000 Km$^2$ of Masirah Island, Oman, has revealed a fully-developed ophiolite complex which is believed to represent a fragment of Cretaceous ocean crust and upper mantle generated at a constructive plate margin. The complex consists of mantle serpentinites, plutonic rocks ranging from dunite to trondhjemite, a sheeted dyke complex and pillow lava-sediment sequences, all of which have been chemically and petrographically analysed. Several belts of serpentinite occur within the ophiolite associated with major fault-lines. The serpentinites are clearly derived from depleted harzburgitic mantle and their field relations suggest that some were emplaced in the oceanic environment. The chemistry of the plutonic rocks suggests that they are products of dominantly open-system fractional crystallisation of tholeiitic liquid(s), possibly in several discrete magma chambers. Modelling of trace and RE elements suggests that moderate degrees of mantle peridotite melting were involved in production of the magma chamber parental liquid(s). At a higher crustal level sheeted dyke-massive gabbro relationships are interpreted in a model of roof underplating, which causes a decreasing frequency of dyke injection. Metamorphism of the sheeted dykes and lavas is interpreted as sub-sea floor in origin and its effect on whole-rock chemistry is assessed. The dykes and lavas have a chemistry largely typical of present-day ocean tholeiites and the relative contributions of the processes of partial melting and fractional crystallisation to that chemistry are evaluated. Two localised volcanic groups were identified, which appear to have enriched chemistries compatible with origin at off -axis oceanic islands. A major tectonic zone cross-cuts the ophiolite units and has features reminiscent of the modern oceanic transform faults. The importance of this structure, both in the oceanic environment and during the process of ophiolite emplacement, is assessed. Intrusive into the ophiolite is a granite whose trace and RE element chemistry is alien to the oceanic environment and suggests melting of continental crust Finally, a synthesized model of the former constructive margin is produced and an attempt is made to define the type of spreading centre represented. Comparison of the Masirah Ophiolite with the Semail Ophiolite of the Oman Mountains suggests that their former correlation may be ill founded. An assessment of late Mesozoic -early Tertiary plate motions indicates an origin during Cretaceous sea-floor spreading of an early Indian Ocean. Several features may indicate a slow-spreading, much-faulted, constructive margin

myCourtroom: Rosie’s family go to court; the use of simulations in preparing social workers for court

The role of social workers in court, how they prepare, train, write and present their reports, has been the focus of much debate. Key messages from research tell us that social workers often find court work stressful; they can lack confidence in writing reports giving evidence and being cross examined. Pre-qualification training in this area can be patchy, with many workers reporting they often learn ‘on the job.’ This article documents the journey from analysing primary and secondary research findings, via a partnership between the University of Kent Centre for Child Protection and Children and Family Court Advisory and Support Service (Cafcass), to develop a training simulation for practitioners to increase their knowledge, preparation and practice for court. The partnership turned these research findings into an interactive, immersive simulation to give practitioners the space to reflect upon and critique their experiences of court. Findings from an initial evaluation of the simulation were positive with participants highly rating its usefulness in developing court room skills and knowledge

Health and lifestyle of Nepalese migrants in the UK

Background: The health status and lifestyle of migrants is often poorer than that of the general population of their host countries. The Nepalese represent a relatively small, but growing, immigrant community in the UK, about whom very little is known in term of public health. Therefore, our study examined the health and lifestyle of Nepalese migrants in the UK. Methods: A cross-sectional survey of Nepalese migrants in UK was conducted in early 2007 using a postal, self-administered questionnaire in England and Scotland (n = 312), and telephone interviews in Wales (n = 15). The total response rate was 68% (327 out of 480). Data were analyzed to establish whether there are associations between socio-economic and lifestyle factors. A multivariate binary logistic regression was applied to find out independent effect of personal factors on health status. Results: The majority of respondents was male (75%), aged between 30 and 45 (66%), married or had a civil partner (83%), had university education (47%) and an annual family income (69%) ranging from £5,035 to £33,300. More than one third (39%) of the respondents have lived in the UK for 1 to 5 years and approximately half (46%) were longer-term residents. Most (95%) were registered with a family doctor, but only 38% with a dentist. A low proportion (14%) of respondents smoked but more than half (61%) consumed alcohol. More than half (57%) did not do regular exercises and nearly one fourth (23%) of respondents rated their health as poor. Self reported 'good' health status of the respondents was independently associated with immigration status and doing regular exercise Conclusion: The self reported health status and lifestyle, health seeking behaviour of Nepalese people who are residing in UK appears to be good. However, the overall regular exercise and dentist registration was rather poor. Health promotion, especially aimed at Nepalese migrants could help encourage them to exercise regularly and assist them to register with a dentist

Are DNA repair factors promising biomarkers for personalized therapy in gastric cancer?

Chronic inflammation is a driving force for gastric carcinogenesis. Reactive oxygen species (ROS) generated during the inflammatory process generates DNA damage that is processed through the DNA repair pathways. In this study, we profiled key DNA repair proteins (single-strand-selective monofunctional uracil-DNA glycosylase 1 [SMUG1], Flap endonuclease 1 [FEN1], X-ray repair cross-complementing gene 1 [XRCC1], and Ataxia telangiectasia mutated [ATM]) involved in ROS-induced oxidative DNA damage repair in gastric cancer and correlated to clinicopathological outcomes. High expression of SMUG1, FEN1, and XRCC1 correlated to high T-stage (T3/T4) (p-values: 0.001, 0.005, and 0.02, respectively). High expression of XRCC1 and FEN1 also correlated to lymph node-positive disease (p-values: 0.009 and 0.02, respectively). High expression of XRCC1, FEN1, and SMUG1 correlated with poor disease-specific survival (DSS) (p-values: 0.001, 0.006, and 0.05, respectively) and poor disease-free survival (DFS) (p-values: 0.001, 0.001, and 0.02, respectively). Low expression of ATM correlated to lymph node positivity (p=0.03), vascular invasion (p=0.05), and perineural invasion (p=0.005) and poor DFS (p=0.001) and poor DSS (p=0.003). In the multivariate Cox model, high XRCC1 and low ATM were independently associated with poor survival (p=0.008 and 0.011, respectively). Our observation supports the hypothesis that DNA repair factors are promising biomarkers for personalized therapy in gastric cancer. Antioxid. Redox Signal. 18, 2392–2398

Genomic and protein expression analysis reveals flap endonuclease 1 (FEN1) as a key biomarker in breast and ovarian cancer

FEN1 has key roles in Okazaki fragment maturation during replication, long patch base excision repair, rescue of stalled replication forks, maintenance of telomere stability and apoptosis. FEN1 may be dysregulated in breast and ovarian cancers and have clinicopathological significance in patients. We comprehensively investigated FEN1 mRNA expression in multiple cohorts of breast cancer [training set (128), test set (249), external validation (1952)]. FEN1 protein expression was evaluated in 568 oestrogen receptor (ER) negative breast cancers, 894 ER positive breast cancers and 156 ovarian epithelial cancers. FEN1 mRNA overexpression was highly significantly associated with high grade (p= 4.89 x 10 - 57) , high mitotic index (p= 5.25 x 10 - 28), pleomorphism (p= 6.31 x 10-19), ER negative (p= 9.02 x 10-35 ), PR negative (p= 9.24 x 10-24 ), triple negative phenotype (p= 6.67 x 10-21) , PAM50.Her2 (p=5.19 x 10-13 ), PAM50.Basal (p=2.7 x 10-41), PAM50.LumB (p=1.56 x 10-26), integrative molecular cluster 1 (intClust.1) ( p=7.47 x 10-12), intClust.5 (p=4.05 x 10-12) and intClust. 10 (p=7.59 x 10-38 ) breast cancers. FEN1 mRNA overexpression is associated with poor breast cancer specific survival in univariate (p=4.4 x 10-16) and multivariate analysis (p=9.19 x 10-7). At the protein level, in ER positive tumours , FEN1 overexpression remains significantly linked to high grade, high mitotic index and pleomorphism (ps< 0.01). In ER negative tumours, high FEN1 is significantly associated with pleomorphism, tumour type, lymphovascular invasion, triple negative phenotype, EGFR and HER2 expression (ps<0.05). In ER positive as well as in ER negative tumours, FEN1 protein over expression is associated with poor survival in univariate and multivariate analysis (ps<0.01). In ovarian epithelial cancers , similarly, FEN1 overexpression is associated with high grade, high stage and poor survival (ps<0.05). We conclude that FEN1 is a promising biomarker in breast and ovarian epithelial cancer